Fabrication of Curcumin and Voriconazole-Loaded Nanosponges Hydrogel for Topical Treatment of Candida albicans: In Vitro, Ex Vivo, and In Vivo Assessments

Voriconazole (VRC) is a new triazole antifungal drug. Curcumin (CRM) is an herbal drug with strong antifungal activity. This study aimed to prepare polymeric nanosponges (NSs) hydrogel for the topical delivery of VRC and CRM as a combination therapy to enhance drugs solubility and deposition within the skin, boost their antifungal activity, and avoid VRC’s side effects. NSs formulae were prepared utilizing different percentages of ethyl cellulose and polyvinyl chloride. 32 Full factorial designs were utilized to select the optimized nanosponges (ONS) which composed of 0.5% EC and 0.5% PVA and showed the minimum PS (155.47 ± 4.65 nm) and PDI (0.34 ± 0.02), and the maximum PY % (71.53 ± 2.01%), ZP (-26.96 ± 1.52 mV), and EE% (72.31 ± 3.42%). The ONS (F1) was amalgamated with CRM in varying ratios and subsequently transformed into three combined NS hydrogels (C1, C2, and C3). C2 showed stronger antifungal activity with 2.91- and 4.16-fold compared to C1 and C3, respectively. The optimized combined NS (C2) showed higher skin deposition by 2.25- and 3.50-fold compared to traditional VRC and CRM hydrogel, respectively. The in vivo microbial count and histopathological studies confirmed the superiority of the antifungal efficacy of C2 hydrogel rather than oral CRM and VRC suspension. Hence, NSs hydrogel can be considered a promising carrier for the topical delivery of VRC and CRM. The promising outcomes of the OCNS hydrogel in the male albino rats highlight the need for further human clinical studies to assess the OCNS hydrogel’s safety and efficacy.